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Adolescent Diabetes and Use of Insulin-like Growth–Factor-1

Am Fam Physician. 1998 May 15;57(10):2536-2539.

Recent studies have emphasized the importance of sustained glycemic control to prevent long-term microvascular complications in patients with type 1 (insulin-dependent) diabetes mellitus. Such control is difficult to achieve in adolescents, partly because the hormonal changes of puberty substantially influence insulin sensitivity. Even with intensive insulin therapy, good glycemic control may be difficult to achieve in adolescents, particularly during the night. Acerini and colleagues conducted a randomized, double-blind, placebo-controlled trial to determine if adding insulin-like growth–factor-1 to insulin therapy in adolescents with type 1 diabetes would improve insulin sensitivity and glycemic control.

The authors studied 53 patients from 10 to 20 years of age (median age: 16 years) with type 1 diabetes mellitus of at least two years' duration who received insulin therapy three to four times a day. The 26 males and 27 females were randomly assigned to one of three groups. Eighteen patients in each of the two treatment groups self-administered insulin-like growth–factor-1 in dosages of 20 or 40 μg per kg daily for 24 weeks. A control group of 17 patients self-administered placebo. Patients were asked to test blood glucose levels twice daily and to adjust insulin dosage accordingly to achieve and maintain ideal blood sugar levels. The investigators maintained close contact with study patients through patient visits and telephone calls every two to four weeks. Routine biochemical measures, including glycated hemoglobin (HbA1c) were assessed every four weeks. Glomerular filtration rates and retinal photographs were taken at the beginning of the study and at 24 weeks, after completion of treatment. Patients were followed for an additional eight weeks after completion of treatment.

The patients in the three groups were comparable in age, body mass index and baseline HbA1c. Six patients withdrew from the study, mainly because of difficulty in following the protocol, leaving 15 patients in the placebo group, 14 patients who received 20 mg per kg of insulin-like growth–factor-1 and 18 patients who received 40 mg per kg of insulin-like growth–factor-1. Concentrations of serum insulin-like growth–factor-1 increased in a dose-response manner in the treatment groups, peaking at week 12. HbA1c levels in patients treated with 40 mg per kg were significantly lower compared with the placebo group, without any associated change in body-mass index, insulin dosage, rate of hypoglycemia or evidence of adverse effect on retinal vasculature or glomerular filtration rate. The greatest change occurred within the first 12 weeks of therapy.

By week 24, levels of insulin-like growth–factor-1 had declined, possibly as a result of compliance problems, and HbA1c levels were not significantly different among the three groups. No significant differences were found among the groups in total daily insulin dosage, body mass index, glomerular filtration rate, number of adverse effects or other biochemical variables.

The authors conclude that insulin-like-growth–factor-1 in a dosage of 40 mg per kg per day as an adjunct to insulin therapy can improve HbA1c values in adolescent patients with type 1 diabetes without obvious adverse effects. They call for further studies to identify patients who can benefit most from this treatment approach and also to identify the optimal dosage of insulin-like growth–factor-1 and duration of treatment. Although the loss of therapeutic effect toward the end of this trial may have been related to compliance problems, the possibility of problems with long-term bioavailability or effectiveness of insulin-like growth–factor-1 cannot be ruled out.